TY - JOUR TI - 3D curvature-instructed endothelial flow response and tissue vascularization AU - Mandrycky, Christian AU - Hadland, Brandon AU - Zheng, Ying T2 - Science Advances AB - Vascularization remains a long-standing challenge in engineering complex tissues. Particularly needed is recapitulating 3D vascular features, including continuous geometries with defined diameter, curvature, and torsion. Here, we developed a spiral microvessel model that allows precise control of curvature and torsion and supports homogeneous tissue perfusion at the centimeter scale. Using this system, we showed proof-of-principle modeling of tumor progression and engineered cardiac tissue vascularization. We demonstrated that 3D curvature induced rotation and mixing under laminar flow, leading to unique phenotypic and transcriptional changes in endothelial cells (ECs). Bulk and single-cell RNA-seq identified specific EC gene clusters in spiral microvessels. These mark a proinflammatory phenotype associated with vascular development and remodeling, and a unique cell cluster expressing genes regulating vascular stability and development. Our results shed light on the role of heterogeneous vascular structures in differential development and pathogenesis and provide previously unavailable tools to potentially improve tissue vascularization and regeneration. Engineered spiral microvessels reveal unique contributions of curvature to EC responses to flow and support tissue perfusion. Engineered spiral microvessels reveal unique contributions of curvature to EC responses to flow and support tissue perfusion. DA - 2020/09/01/ PY - 2020 DO - 10.1126/sciadv.abb3629 DP - advances.sciencemag.org VL - 6 IS - 38 SP - eabb3629 LA - en SN - 2375-2548 UR - https://advances.sciencemag.org/content/6/38/eabb3629 Y2 - 2020/09/17/18:10:31 ER -